Composition and topical formulation of antiandrogens of natural (plant) origin

ABSTRACT

A composition consisting essentially of a plant extract rich in antiandrogenic sterols from dwarfpalms, African plums, willow herbs, nettle herbs, or hops. The composition can be combined with an acceptable carrier agent to form a variety of topical formulations for cosmetic and pharmaceutical purposes.

TECHNICAL SPHERE OF THE INVENTION

The present invention fits in the technical sphere of hormonal and/orantihormonal therapy, destinated to the maintenance of certain functionsand structures that deteriorate with aging or due to other reasons andthe treatment of several metabolic or degenerative illnesses and controlof the growth, aspect, development and/or growth of certain structures,such as hair (excess or loss), corporal hair, prostate, skin and itsproblems (acne, rosacea . . . ), etc. which are influenced by the sexhormones levels (androgens and estrogens).

More exactly, the present invention refers to a new form of presentationfor phytosterols with antiandrogenic action destinated to percutaneoustopical application with cosmetic and/or pharmaceutical purposes.

STATE OF THE TECHNIC PREVIOUS TO THE INVENTION

The natural serols present and extracted from vegetal drugs, such as:

Serenoa sp. pl. Fam. Palmaccae. Spanish denomination: Sabal, palmeras deFlorida, de Tejas y de Cuba. English den . . . Dwarfpalm. French Den.:Sabals, Serenoas. German Den.: Zwergpalmes, Sagepalmes. Italian Den.:Sabali.

Pygeum sp. pl. Fam. Rosaceae. Spanish Denomination: Ciruelos africanos.English Den.: African plums, French Den.: Pruniers d'Afrique. ItalianDen.: Prune di Africa.

Epilobium sp. pl. Fam. Oenoteraccae. Spanish denomination: Epliobios.English Den.: Willow herbs, Rosebay. French Den.: Epliobes. German Den.:Waldroschens. Italian Den.: Epilobii.

Urtica dioica L. y Urtica sp. pl. Fam. Urticaceae. Spanish denomination:Ortigas mayores. English Den.: Nettle herbs, urtica y stinging nettles.German Den.: Brennesselkrauts, Haarnesselkrauts, Hanfnesselkrauts.French Den.: Herbes d'ortie. Italian Den.: Ortiche.

Hypoxis, sp. pl., specially the root of the Hypoxis rooperi and Hypoxisbrasiliensis.

Cucurbita, sp. pl., Fam. Cucurbitaceae, specially the seeds ofCurcurbita pepo y Cucurbita maxima (spanish, popular denomination:calabazas).

And other vegetal products such as bitter resins present in the strobilaof Hop (Humulus lupulus L.; Fam Cannabaceao), also with antiandrogenicaction are used in medicine orally for the treatment of prostate benignhypertrophy and other prostatic problems, femenin hirsutism andvirilism.

Several of the vegetal extracts, rich in phytosterols, mentioned before,are being used orally as pharmaceutical specialities for the treatmentof prostatic benign hypertrophy (Adriazola et al., 1992, Di-Silverio etal., 1992, Vahlensiek et al., 1993, Timmermans et al., 1990, Muhlbauer,1991, Breu et al., 1992 y Sultan et al, 1984).

DESCRIPTION IN DETAIL OF THE INVENTION

The present invention, as exposed before, makes reference to a newcosmetic and pharmaceutical formulation based on extracts and galenicconcentrates from vegetal drugs rich in sterols and/or others compounds(resins, etc.) with antiandrogenic action, for their percutaneoustopical application.

The applicant has been able to verify, through his investigations, thatthe active principes of these vegetal drugs and specially thephytosterols and resin, etc. are absorbed well topically, mainlypercutaneously.

Therefore, and accordingly to this finding, the inventors propose anovel cosmetic or pharmaceutical formule of presentation (topical) ofthese vegetal extracts, that we following enumerate:

Glycolic extracts of Dwarfpalms, of African plums, of Willow herbs, ofNettle herbs and of Hops.

Glyceric extracts of Dwarfpalms, of African plums, of Willow gerbs, ofNettle herbs and of Hops.

Hydroalcoholic extracts of Dwarfpalms, African plums, of Willow herbs,of Nettle herbs or Hops.

Lipidic-sterolic extracts of Dwarfpalms, of African plums, of Willowherbs, of Nettle herbs and of Hops.

Acetic extracts (vinegars) of Dwarfpalms, of African plums, of Willowherbs, of Nettle herbs and of Hops.

Chloroformic and ethereal extracts of Dwarfpalms, of African plums, ofWillow herbs, of Nettle herbs and of Hops.

Dry extracts (and soft) of Dwarfpalms, of African plums, of Willowherbs, of Nettle herbs and of Hops.

All these extracts, individually or combined, would became part ofdifferent preparations for topical application, such as gels, O/W andW/O emulsions, solutions or ointments for percutaneous application withcosmetic or pharmaceutical purposes.

This type of applications allows to reach topically the more convenientlevels of these vegetal principles for each problem.

The new formulation of the invention is characterized for containing asessential ingredients for COSMETICS:

a) Between 0.1 and 10% of glycolic or glyceric extracts or oleates ofDwarfpalms, of African plums, of Willow herbs, of Nettle herbs and ofHops.

b) As acrylic gel (Carbopol between 0.5 and 3%), gels derivated fromguar-gum (Between 1 and 3%), gels derivated from cellulose (from 1 to5%), o/w emulsions (specially with L-200 base, between 12 and 18%,purcelin oil, between 18 and 25%), w/o emulsions (specially Cold-Cream)and hydroalcoholic, hydropropylenglycolic, hydroglyceroalcoholicsolutions with an alcoholic content between 3 and 80° and hydroglycolicsolutions.

Besides these ingredients a) and b), these formulations can containserera vegetal extracts with cooperating or complementary effects, whichcould be glycolic, hydroglycerolic, hydroalcoholic andhydropropylenglycolic extracts, in proportions between 0.1 and 20%menthol, mentil lactate, mint essence, etc.); Astrigent vasoconstrictingextracts of Witch-hazel, Ladies' mantle and Rantany; Demulcent extractsof Aloe, Oats, Althea, Camomile, Yarrow and Mallow: Antiseptic extractsof Hops and other active ingredients; anti-free radicals (tocopherols,between 0.05 and 0.1%, L-ascorbic acid, between 0.1 and 5%,cytoflavonoids, between 0.1 and 2%); antiinflammatories: Allantoin andderivatives (between 0.05 and 0.2%), alfa-bisalobol, between 0.05 and0.2%, azulene and derivatives (between 0.05 and 0.2%); antisweatingagents: Aluminium salts, specially Aluminium clorhydroxide between 0.1and 5% and desiccated aluminium hydroxide collodial gel, between 0.1 and10% and the glycolic, glyceric or fluid extract of Sage, between 0.1 and5%; vegetal proteolytic enzimes, specially papain between 0.1 and 2%,bromelain, between 0.1 and 0.5%; antialopecia products, such asprogesterone (between 1 and 3%) minoxidil (from 1-3%), tricopeptides(0.01-2%) and tricosacarides (0.1-2%), hair decolorants, speciallymandarin essential oil (0.5-5%) and other hair growth retardingsubstances, such as alkyl-isoquinoleine bromide (0.2-3%).

The new formulation of the invention is characterized for itscomposition as essential ingredients for PHARMACY:

a) Between 0.1 and 100% of glycolic extracts of de Dwarfpalms, Africanplum, Willow herbs, Nettle herbs and Hops. Between 0.1 and 30% of fluidextract of Dwarfpalm, of African plum, of Willow herb, of Nettle herband of Hops, or between 0.1 and 100% of glyceric extracts and oleates ofthe same vegetals. Lipidic-sterolic extracts between 0.01 and 2% ordried extracts, between 0.1 and 4%.

b) As acrylic gel (Carbopol between 0.5 and 3%), Guar-gum derivated gels(from 1 to 3%), cellulose derivated gels from 1 to 5%) o/w emulsions(specially with L-200 base, between 12 and 18%, purcelin oil, between 18and 25%), w/o emulsions (specially Cold Cream), hydroalcoholic,hydropropylenalcoholic, and hydroglyerolalcoholic solutions with andalcoholic content between 3 and 80° and hydroglycolic solutions.

Besides these ingredients a) and b), these formulations can containseveral vegetal extracts with cooperating or complementary effects,which could be glycolic, hydroglycerolic, hydroalcoholic andhydropropylenglycolic extracts, in proportion between 0.1 and 20%:Antipruriginous extracts of Centella Asiatica and of Mint andderivatives (asiaticosides, menthol, menthil lactate, mint essence,etc.); Astrigent vasoconstricting extracts of Witch-hazel, Ladies'mantle, and Rantnay; domulcent extracts of Aloe, Oats, Althea, Camomile,Yarrow and Mallow (between 1-15%); Antiseptic extracts of Hops (0.1-10%)and other active ingredients:anti-free radicals (tocopherols, between0.05 and 0.1%, L-ascorbic acid, between 0.1 and 5%, cytoflavonoids,between 0.1 and 2%); antiinflammatories: Allantoin and derivatives(between 0.05 and 0.2%), alfa-bisalobol, between 0.05 and 0.2%, azuleneand derivatives (between 0.05 and 0.2%); corticosteroids (between 0.01and 0.1%); bencidamine Cl' (0.1-0.2%) antisweating agents: Aluminiumsalts, specially Aluminium clorhydroxide between 0.1 and 5% anddesiceated aluminium hydroxide collodial gel, between 0.1 and 10% andthe glycolic, glyceric or fluide extract of Sage, between 0.1 and 5%;vegetal proteolytic enzymes, specially papain between 0.1 and 2%,bromclain, between 0.1 and 0.5%; antialopecia products, such asprogesterone (between 1 and 3%), minoxidil (from 1-3%), tricopeptides(0.01-2%) and tricosacarides (0.1-2%, hair decolorants, speciallymandarin essential oil (0.5-5%) and basic hydroquinone (1-3%); topicaluse antibiotics, specially basic erythromicin (1-3%), and clindamicin(0.5-1%); Keratolytic₋₋ reducting agents, such as salicylic acid andderivatives (0.1-3%), benzoyl peroxide (2.5-10%) and resorcinol(0.1-0.5%); chemical depilatories, such as thioglycolic acid and itssalts (3-10%) and the association with other chemical antiandrogens(cyproterone acetate. Flutemide and Finastiride. Casodex, etc. between0.01 and 2%) and other hair growth retarding substances, such asalkyl-soquinoleine bromide (0.2-5%).

Forms of Performing the Invention

The present invention is illustrated besides by mean of the followingexamples, that do not limit its possibilities: COSMETICS

EXAMPLE 1

In this part we show several formulations according to the presentinvention, indicating the quantities of active ingredients used and theapplication to which they are thought for.

Formulation 1

Glycolic extract of Willow herbs or of nettle herbs

roots or of dwarfpalms or of African plums 7-10%

Alantoin 0.1%

Colorless fluid extract of witch-hazel 10%

alfa-Bisalobol 0.1%

Essential Camomile oil 1%

Essential Mandarin oil 2%

L-Ascorbic Acid 0.2%

Wheat germ oil 3%

Menthil Lactate 0.05%

Hops fluid extract 2%

Acrylic Gel (of Carbopol), sufficient quantity for (csp) 100 g

This formulation is useful for the control and retardation of hairgrowth; this formulation can be also prepared as an hydroalcoholicsolution form.

Formulation 2

Glycolic extract of Willow herbs or of nettle herbs

roots or of dwarfpalms or of African plums 5-7%

Desiccated Aluminum hydroxide Gel 5%

Hops glycolic extract 2-3%

Oats glycolic extract 5%

Plantain glycolic extract 2%

Glycolic extract of Althea 2%

Roses distilled water 10%

Lavender essential oil 2%

Alantoin 0.1%

alfa-Bisalobol 0.1%

Colorless fluid extract of Witch-hazel 5%

Glycolic extract of Centella 2%

Acrylic gel (of Carbopol), csp 100 g

This formulation is useful to control the odor and axillary sweating,besides controlling and retarding the growth of axillary hair. Thisformulation can be also presented as an hydroalcoholic solution form.

Formulacion 3

Glycolic extract of Willow herbs or of nettle herbs

roots or of dwarfpalms or of African plums 5-8%

Hops glycolic extract 2%

plantain glycolic extract 3%

Oat glycolic extract 3%

Glycolic extract of Althea 3%

Colorless fluid extract of Witch-hazel 5-10%

Ulmaria fluid extract 2%

Alantoin 0.1%

Roses distilled water 10%

70° alcohol, csp 100 g

this formulation is useful for controlling hirsutism and acne vulgaris.It can also be presented as a gel (Carbopol or hydroxipropil Guar-Gum).

Formulation 4

Glycolic extract of Nettle herb roots or Willow herb 10%

Tricopeptides 0.1%

Minoxidil 1%

alfa-Bisalobol 0.1%

Hydroalcoholic solucion, csp 100 g

This formulation is useful for control and retardation of hair loss incertain androgenic alopeciae. This formulation can be also presented asa shampoo (anionic sulfonate detergent, csp 100 g).

Pharmaceutical Applications

The present invention is shown additionally by mean of the followingexamples, that do not limit its scope:

EXAMPLE 2

In this example we show several formulations according to the presentinvention, indicating the quantities of active ingredients used andtheir applications:

Formulacion 1

Glycolic extract of Willow herbs or roots of Nettle herbs or ofDwarfpalms or of African plum 8-100%

L-Ascorbic acid, csp (as anti-free radicals)

This formulation is useful for treating hirsutism.

Formulation 2

Fluid extract of Willow herbs or roots of Nettle herbs or of Dwarfpalmsor of African plum 8-25%

L-Ascorbic acid 0.5%

Colorless fluid extract of Witch-hazel 10%

Menthil lactate 0.1%

Wheat germ oil 3%

alfa-Bisalobol 0.1%

Alantoin 0.1%

Mandarin essence 2%

Camomile extract 2%

Hops fluid extract 1%

Acrylic gel (of Cabopol), csp 100 g

This formulation is useful in the treatment of hirsutism. It can also beformulated as an hydroalcoholic solution and in case it is usedimmediately after depilation it can contain papain from 0.5 to 1%.

Formulation 3

Lipidic-sterolic extract of Willow herbs or roots of Nettle herbs or ofDwarfpalms or of African plum 0.2%

alfa-Bisalobol 0.1%

Alantoin 0.1%

Camomile essential oil 1%

Mandarin essential 2%

Colorless fluid extract of Witch-hazel 5%

Hops fluid extract 1%

Acrylic gel (of Carbopol), csp 100 g

This formulation is useful for the treatment of hirsutism and of beningprostatic adenoma (topical use).

Formulation 4

Glycolic extracts of Willow herbs or roots of Nettle herbs or ofDwarfpalms or of African plum 5%

Erythromicin base 2%

L-Ascorbic acid 0.5%

Glycolic extract of Plantain 3%

Elder-tree distilled water 5%

Hops fluid extract 1%

Hydroalcoholic solution, csp 100 g

This formulation is useful for treating acne vulgaris and rosacea acne.

Formulation 5

Fluid extract of Willow herbs or roots of Nettle herbs of Dwarfpalms orof African plum 7%

Benzoyl peroxide 5%

L-Ascorbic acid 0.2%

alfa-Bisalobol 0.1%

Glycolic extract of Aloe 3%

Glycolic extract of Althea 3%

Hops fluid extract 1%

Acrylic gel (of Carbopol, csp 100 g

This formulation is useful for treating acne.

Formulation 6

Fluid extract of Willow herbs or roots of Nettle herbs of Dwarfpalms orof African plum 10%

Benzoyl peroxide 5%

L-Ascorbic acid 0.3%

alfa-Bisalobol 0.1%

Glycolic extract of Plantain 5%

Oat glycolic extract 10%

Glycolic extract of Althea 5%

Triamcianolone acetonide 0.05%

Hops glycolic extract 1%

Acrylic gel (of Carbopol), csp 100 g

This formulation is useful for treating acne.

Formulation 7

Fluid extract of Willow herbs or roots of Nettle herbs of Dwarfpalms orof African plum 5-10%

Clindamicine 1%

L-Ascorbic acid 0.2%

Glycolic extract of Althea 5%

Menthil lactate 0.1%

Hops glycolic extract 1%

Acrylic gel (of Carbopol) or hydroalcoholic solution, csp 100 g

This formulation is useful for treating acne.

L-Ascorbic acid 0.2%

Glycolic extract of Althea 5%

Menthil lactate 0.1%

Hops glycolic extract 1%

Acrylic gel (of Carbopol) or hydroalcoholic solution, csp 100 g

This formulation is useful for treating acne.

What is claimed is:
 1. A topical formulation comprising about 10% byweight of a glycolic plant extract rich in antiandrogenic sterolsselected from a group consisting of nettle herb roots or willow herbs incombination with a cosmetically acceptable vehicle and further incombination with an antialopecia agent.
 2. The cosmetic of claim 1,wherein said cosmetically acceptable vehicle is a hydroalcoholicsolution.
 3. A cosmetic for topical application to the skin to controland retard hair loss, comprising about 10% by weight of a glycolic plantextract rich in antiandrogenic sterols selected from a group consistingof nettle herb roots and willow herbs in combination with a cosmeticallyacceptable carrier and an antialopecia agent.
 4. A method for treating asubject with hirsutism comprising the step of:administering atherapeutically effective amount of a transdermal medicament comprisinga topical formulation including a plant extract rich in antiandrogenicsterols selected from a group consisting of willow herbs, nettle herbroots, dwarfpalms or African plums in combination with a carrier agentto an affected area of the subject.
 5. A method for controlling andretarding hair loss in a subject comprising the step of:administering atopical formulation comprising a plant extract rich in antiandrogenicsterols selected from a group consisting of nettle herb roots or willowherbs in combination with a cosmetically acceptable vehicle to anaffected area of the subject.
 6. A method for controlling and retardinghair growth in a subject comprising the step of:administering a topicalformulation comprising a plant extract rich in antiandrogenic sterolsselected from a group consisting of willow herbs, nettle herb roots,dwarfpalms, or African plums in combination with a cosmeticallyacceptable vehicle to an affected area of the subject.
 7. The method fortreating a subject with hirsutism according to claim 4, wherein saidtransdermal medicament comprises from about 8 to 100% by weight of saidplant extract and wherein said plant extract is glycolic.
 8. The methodfor treating a subject with hirsutism according to claim 4, wherein saidtransdermal medicament comprises from about 8 to 25% by weight of saidplant extract and wherein said plant extract is fluidic.
 9. The methodfor treating a subject with hirsutism according to claim 4, wherein saidtransdermal medicament comprises about 0.2% to 2% by weight of saidplant extract and wherein said plant extract is lipidic-sterolic. 10.The method for controlling and retarding hair loss in a subjectaccording to claim 5, wherein said topical formulation comprises about10% to 20% by weight of said plant extract and wherein said plantextract is glycolic.
 11. The method for controlling and retarding hairloss in a subject according to claim 10, wherein said topicalformulation is further in combination with an antialopecia agent. 12.The method for controlling and retarding hair loss in a subjectaccording to claim 11, wherein said cosmetically acceptable vehicle is ahydroalcoholic solution.
 13. A method for controlling and retarding hairloss in a subject comprising the step of:administering a cosmetic fortopical application to the skin comprising about 10% to 20% by weight ofa glycolic plant extract rich in antiandrogenic sterols selected from agroup consisting of nettle herb roots and willow herbs in combinationwith a cosmetically acceptable vehicle and an antialopecia agent to anaffected area of the subject.
 14. The method for controlling andretarding hair growth in a subject according to claim 6, wherein saidtopical formulation comprises about 7 to 10% by weight of said plantextract and wherein said plant extract is glycolic.
 15. The method forcontrolling and retarding hair growth in a subject according to claim14, wherein said cosmetically acceptable vehicle is an acrylic gel or acream.